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The study examined the possibility that organic calcium channel blockers alter autonomic nervous system function by acting on brainstem neurons. Intracisternal administration of diltiazem or verapamil produced dose-related decreases in arterial pressure and heart rate. Diltiazem administered by drop on the dorsal surface of the brainstem at the obex or microinjected directly into the nucleus tractus solitarius also decreased arterial pressure and heart rate. The responses were absent or markedly attenuated in rats previously treated with 6-hydroxydopamine or with bilateral electrolytic lesions of the nucleus tractus solitarius but were preserved in rats treated with atropine or with sham nucleus tractus solitarius lesions. Nifedipine or ethylene glycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid administered on the dorsal surface of the brainstem at the obex decreased arterial pressure and heart rate. Vehicle, acid saline, or sucrose solution failed to alter arterial pressure or heart rate. These results suggest that organic calcium channel blockers produce excitation of the nucleus tractus solitarius neurons, directly or indirectly, which results in the withdrawal of sympathetic nervous activity and in the decrease in arterial pressure and heart rate. The results suggest that calcium ion plays an important role in maintaining integral function of neurons in the brainstem, particularly in the nucleus tractus solitarius.

Arterial pressure and heart rate responses to calcium channel blockers administered in the brainstem in rats.